1. Field of the Invention
The present invention relates to a method of making a solid oral dosage form attached to a handle by use of high frequency mechanical vibrations. The present invention also relates to a method of attaching a handle to a solid oral dosage form, the method comprising: (a) placing the handle in contact with the solid oral dosage form, wherein an area of contact between the handle and the solid oral dosage form forms a joint interface; (b) applying high frequency mechanical vibrations to the joint interface until the solid oral dosage form at the joint interface reaches a molten state; and (c) cooling the joint interface in a molten state to allow solidification, thereby attaching the handle to the solid oral dosage form.
2. Background Art
Numerous active agent delivery forms exist for administration of active agents to a subject. The majority of active agents are administered either via (1) oral administration to the gastrointestinal (GI) tract by ingestible tablets or capsules or (2) by injection. Neither of these administration routes are effective in all cases, and both administration routes suffer from several disadvantages.
For oral administration to the GI tract, one disadvantage is that there is normally a substantial delay between the time of oral administration and the time that the therapeutic effect of the active agent begins. Another difficulty encountered in administering active agents orally to the GI tract is that dosages are prepared or determined for use with an “average” patient. Most active agents have widely varying effects on different patients. The result can be underdosing or overdosing a particular patient.
Additionally, there are disadvantages associated with injections. Many patients, particularly children and geriatric adults, have an aversion to injections. In some patients, this aversion can be so pronounced as to make the use of injections a serious concern. Since intense psychological stress can exacerbate a patient's debilitated condition, it sometimes becomes undesirable to use injections where the patient is seriously ill or suffers from a debilitating condition or injury.
As an alternative to administration to the GI tract and injections, administration to the mucosa of the oral cavity has been used. One advantage of oral mucosa delivery is that it is a non-invasive active agent delivery method that can be administered by the caregiver or the patient with minimal discomfort. Furthermore, oral mucosa delivery has better patient compliance, less risk of infection and lower cost than invasive procedures such as injection and implantation. It also has a much shorter onset time, i.e., the time from administration to therapeutic effect, than does oral delivery to the GI tract. An active agent absorbed via the oral mucosa will also avoid first pass metabolism, in which the active agent is metabolized in the GI tract and liver.
Administration of active agents via the oral mucosa does not expose the active agent to the gastric and intestinal digestive juices. Commercial examples of active agent formulations delivered via the oral mucosa include Oralet® (Abbott Laboratories, Abbott Park, Ill.) and Actiq® (Cephalon Inc., Salt Lake City, Utah).
Oral transmucosal delivery forms, such as sublingual tablets, troches, lozenges, lozenges-on-a-stick, chewing gums, and buccal patches, have been described previously. U.S. Pat. No. 5,711,961 to Reiner, et al. discloses a chewing gum for delivery of active agents. Oral transmucosal delivery using a buccal patch is disclosed in U.S. Pat. No. 5,298,256 to Flockhart, et al. Lozenges and tablets are commonly used for oral transmucosal delivery of active agents. For example, nitroglycerin sublingual tablets have been on the market for many years.
A solid oral dosage form attached to a handle, a.k.a., a lollipop or lozenge-on-a-stick, for transmucosal active agent delivery is disclosed in U.S. Pat. No. 4,671,953. In addition to being non-invasive and providing a particularly easy method of delivery, the solid oral dosage form attached to a handle allows a patient or caregiver to move the dose in and out of the mouth to titrate the dose. This practice is called dose-to-effect, in which a patient or caregiver controls the administration of the dose until the expected therapeutic effect is achieved. The practice of dose-to-effect is particularly important for certain symptoms, such as pain, nausea, motion sickness, and premedication prior to anesthesia because each patient needs a different amount of medication to treat these symptoms. Once the appropriate amount of active agent is delivered, the patient or caregiver can remove the solid oral dosage form, thus stopping the active agent delivery to prevent overdose.
A common concern with medicated solid oral dosage forms attached to a handle is the possibility that the solid oral dosage form part of the device will become detached from the handle. If the solid oral dosage form becomes detached from the handle, then it can be more difficult to remove and/or administer the active agent as desired. Also of concern is the possibility that the solid oral dosage form which is detached from its handle could be swallowed in its entirety, possibly resulting in an overdosing of the active agent. Similarly, a detached solid oral dosage form could also become a choking hazard.